An immunohistologic study was performed on temporal bones from 30 LP/J mice and 17 CBA/J mice to assess the role of immunologic injury in the pathogenesis of dysplastic bony lesions in LP/J mice. Temporal bones were harvested from animals aged 2 to 31 months to evaluate the progression of the disease. As early as 2 months of age, before the onset of bony lesions, the tympanic cavities frequently contained small effusions coating the ossicles and otic capsules that were demonstrated to contain immunoglobulins and pockets of macrophages. Later in the course of the disease, bony lesions grossly and histologically similar to human otosclerosis developed, which stained for immunoglobulins. No similar bony lesions, effusions, cellular infiltrates, or staining for immunoglobulins was detected in the control animals, even in the presence of acute otitis media. This study suggests a role of immunologic injury in the pathogenesis of dysplastic bony lesions in LP/J mice.